The University of Colorado Cancer Center proposes to establish a Specialized Program in Research Excellence (SPORE) in Lung cancer to expand our understanding of the biology of lung cancer, to find new methods of diagnosis, prevention and treatment and to serve as a regional, national and international resource for the study of lung cancer. As a part of this SPORE application we will conduct interrelating research projects, 8 clinical trials and support the 5 cores, the career development of 4 young investigators and the recruitment of new investigators with special research capabilities. Our research studies will focus on abnormalities in growth factors pathways, changes in preneoplastic epithelium, and abnormalities in lung cancer cells. This will include the study of oncogenes and suppressor genes and methods to reverse abnormalities. We will define intermediate markers associated with premalignant lesions and whether these markers change in response to discontinuation of smoking, retinoic acid therapy or other chemopreventive measures. We will study agents which interfere with lung cancer signal transduction and determine whether these are safe and useful for the treatment or prevention of lung cancer. We will assess strategies to stop cigarette consumption with high risk patients and the effects this has on intermediate markers. We will establish new clinical protocols and conduct them alone or in collaboration with other institutions. We will establish two "Banks" of tissues: 1) a premalignant bank to include sputum and bronchial biopsies, bronchial brushings, bronchial lavage and urine; 2) a malignant bank to include tumor tissue, adjacent lung serum, and lymphocytes. These tissues will be studied by our investigators and made available to the scientific community on a peer-reviewed/availability basis. We will collaborate with other lung cancer SPORES and lung cancer investigators to reach our goals.